Vyletelová V, Nováková M, Pašková Ľ. Alterations of HDL's to piHDL's Proteome in Patients with Chronic Inflammatory Diseases, and HDL-Targeted Therapies. Pharmaceuticals (Basel). 2022 Oct 18;15(10):1278. doi: 10.3390/ph15101278. PMID: 36297390; PMCID: PMC9611871.

Nováková M, Vyletelová V, Hlubinová B, Kiňová Sepová H, Pašková Ľ. Impact of culture medium on the interpretation of qRT-PCR data in HepG2 incubated with lactobacilli. Lett Appl Microbiol. 2024 Jun 3;77(6):ovae050. doi: 10.1093/lambio/ovae050. PMID: 38806242.

Chrastina M, Poništ S, Tóth J, Czigle S, Pašková Ľ, Vyletelová V, Švík K, Bauerová K. Combination Therapy of Carnosic Acid and Methotrexate Effectively Suppressed the Inflammatory Markers and Oxidative Stress in Experimental Arthritis. Molecules. 2022 Oct 21;27(20):7115. doi: 10.3390/molecules27207115. PMID: 36296709; PMCID: PMC9612293.

Pružinská K, Chrastina M, Khademnematolahi S, Vyletelová V, Gajdošová L, Pastvová L, Dráfi F, Poništ S, Pašková Ľ, Kucharská J, Sumbalová Z, Muchová J, Martiniaková S, Bauerová K. Astaxanthin, Compared to Other Carotenoids, Increases the Efficacy of Methotrexate in Rat Adjuvant Arthritis. Int J Mol Sci. 2024 Aug 9;25(16):8710. doi: 10.3390/ijms25168710. PMID: 39201397; PMCID: PMC11354740.

Vyletelová V, Nováková M, Pašková Ľ. Alterations of HDL's to piHDL's Proteome in Patients with Chronic Inflammatory Diseases, and HDL-Targeted Therapies. Pharmaceuticals (Basel). 2022 Oct 18;15(10):1278. doi: 10.3390/ph15101278. PMID: 36297390; PMCID: PMC9611871.

Nováková M, Vyletelová V, Hlubinová B, Kiňová Sepová H, Pašková Ľ. Impact of culture medium on the interpretation of qRT-PCR data in HepG2 incubated with lactobacilli. Lett Appl Microbiol. 2024 Jun 3;77(6):ovae050. doi: 10.1093/lambio/ovae050. PMID: 38806242.

Chrastina M, Poništ S, Tóth J, Czigle S, Pašková Ľ, Vyletelová V, Švík K, Bauerová K. Combination Therapy of Carnosic Acid and Methotrexate Effectively Suppressed the Inflammatory Markers and Oxidative Stress in Experimental Arthritis. Molecules. 2022 Oct 21;27(20):7115. doi: 10.3390/molecules27207115. PMID: 36296709; PMCID: PMC9612293.

Pružinská K, Chrastina M, Khademnematolahi S, Vyletelová V, Gajdošová L, Pastvová L, Dráfi F, Poništ S, Pašková Ľ, Kucharská J, Sumbalová Z, Muchová J, Martiniaková S, Bauerová K. Astaxanthin, Compared to Other Carotenoids, Increases the Efficacy of Methotrexate in Rat Adjuvant Arthritis. Int J Mol Sci. 2024 Aug 9;25(16):8710. doi: 10.3390/ijms25168710. PMID: 39201397; PMCID: PMC11354740.

Hu S, Zhu Y, Zhao X, Li R, Shao G, Gong D, Hu C, Liu H, Xu K, Liu C, Xu M, Zhao Z, Li T, Hu Z, Shao M, Liu J, Li X, Wu H, Li J, Xu Y. Hepatocytic lipocalin-2 controls HDL metabolism and atherosclerosis via Nedd4-1-SR-BI axis in mice. Dev Cell. 2023 Nov 6;58(21):2326-2337.e5. doi: 10.1016/j.devcel.2023.09.007. Epub 2023 Oct 19. PMID: 37863040.

Al-Kuraishy HM, Hussien NR, Al-Niemi MS, Fahad EH, Al-Buhadily AK, Al-Gareeb AI, Al-Hamash SM, Tsagkaris C, Papadakis M, Alexiou A, Batiha GE. SARS-CoV-2 induced HDL dysfunction may affect the host's response to and recovery from COVID-19. Immun Inflamm Dis. 2023 May;11(5):e861. doi: 10.1002/iid3.861. PMID: 37249296; PMCID: PMC10187021.

Azúa-López ZR, Pezzotti MR, González-Díaz Á, Meilhac O, Ureña J, Amaya-Villar R, Castellano A, Varela LM. HDL anti-inflammatory function is impaired and associated with high SAA1 and low APOA4 levels in aneurysmal subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2023 Nov;43(11):1919-1930. doi: 10.1177/0271678X231184806. Epub 2023 Jun 26. PMID: 37357772; PMCID: PMC10676137.

Habtemariam S. Anti-Inflammatory Therapeutic Mechanisms of Natural Products: Insight from Rosemary Diterpenes, Carnosic Acid and Carnosol. Biomedicines. 2023 Feb 13;11(2):545. doi: 10.3390/biomedicines11020545. PMID: 36831081; PMCID: PMC9953345.

Mitrović J, Hrkač S, Tečer J, Golob M, Ljilja Posavec A, Kolar Mitrović H, Grgurević L. Pathogenesis of Extraarticular Manifestations in Rheumatoid Arthritis-A Comprehensive Review. Biomedicines. 2023 Apr 24;11(5):1262. doi: 10.3390/biomedicines11051262. PMID: 37238933; PMCID: PMC10216027.

GUKPOST/14/2025: The Effect of Rapamycin and Everolimus in a Model of THP-1 Conditioned Medium–Stimulated HepG2 Cells

In chronic inflammatory diseases (CIDs), alterations in lipid metabolism frequently occur as a result of systemic inflammation, increasing susceptibility to atherosclerosis and cardiovascular mortality. Understanding inflammation-driven metabolic changes may contribute to improving cardiovascular health in patients with CIDs. Rapamycin and everolimus, selective mTOR inhibitors, are commonly used to study mTOR signaling. This study aims to assess how mTOR inhibition affects inflammation-induced changes in vitro, using a model of HepG2 cells stimulated with conditioned medium (CM) as a complex inflammatory model. Previous results obtained from this model suggest the involvement of mTOR in the modulation of lipid metabolism during inflammation, and its inhibition by rapalogs may therefore contribute to a better understanding of the role of mTOR in this process.Conditioned medium will be prepared by differentiating THP-1 monocytes into macrophages, which will subsequently be stimulated with lipopolysaccharide. The CM will then be applied to HepG2 cells to simulate an inflammatory environment. Following mTOR inhibition with rapalogs, their effects on downstream mTOR effectors and target genes in CM-stimulated HepG2 cells will be analyzed. mRNA and protein expression levels of target genes and mTOR effectors will be evaluated using quantitative PCR and Western blotting, respectively. To further elucidate the mechanisms underlying this remodeling, transfection techniques will also be employed.

Role: Principal Investigator

GVRFaFUK/1/2025: Therapeutic Potential of Hepatocyte Growth Factor in Immunometabolic Disorders: Implications for Diabetes Mellitus and Rheumatoid Arthritis

Immunity and metabolism are closely interconnected. Inflammation is involved in the primary pathogenesis of numerous diseases, such as rheumatoid arthritis (RA), as well as in diseases whose initial cause lies elsewhere, such as diabetes mellitus (DM). The progression of inflammation contributes to the development of complications and is closely associated with disruption of metabolic pathways.Hepatocyte growth factor (HGF) can interfere with the regulation of both inflammation and metabolism; therefore, we consider it a potentially suitable therapeutic target at the interface between immunity and metabolism, with possible application in the treatment of immunometabolic disorders such as DM and RA. In this project, we have defined several specific aims: 1. To identify the role of HGF in organs involved in lipid metabolism that are most affected by DM (adipose tissue, liver, skeletal muscle), with a focus on inflammation and related processes in an animal model of DM. 2. To investigate the activity of the HGF cascade in the liver of animals with adjuvant arthritis (AA). 3. To test the effect of HGF in vitro under conditions of simulated hyperglycemic and/or inflammatory stimulation in cell models (HepG2, 3T3, SW-872). 4.To examine the above characteristics in vitro under conditions of HGF or HGF receptor blockade during inflammation and hyperglycemia.

Role: Principal Investigator for KBMBL

VEGA 2/0115/19 New approaches to the treatment of cachexia, inflammation and oxidative stress in experimental arthritis: The effect of various plant extracts of olive leaves, Rhodiola rosea, Tribulus terrestris, and Extra Virgin Olive Oil

The project focused on testing the effectiveness of various natural substances in alleviating the symptoms of inflammation and associated pathologies in a model of adjuvant arthritis in rats. Our contribution involved testing liver samples using the quantitative real-time PCR method, where we monitored changes in various inflammatory, antioxidant, and other genes expression.

Role: active participant (laboratory work)

VEGA 1/0429/21: Study of modulation mechanisms of inflammation and lipid metabolism by lactobacilli in the model of nonalcoholic fatty liver disease

The project is focused on studying the mechanisms of action of four Lactobacillus strains (i) on the inflammatory process and lipid metabolism in a liver model (HepG2) and (ii) on the impaired intestinal barrier (Caco-2) under in vitro conditions. In the first phase, we will focus on studying the TLR4 signaling pathway and its downstream molecules, the activation of anti-inflammatory cytokine production, and the stimulation of the expression of negative regulators of the TLR4 signaling pathway in the liver. We will monitor the impact of Lactobacilli on the regulation of lipid metabolism (influx, efflux, synthesis, and degradation of cholesterol, triacylglycerols, and fatty acids). In the second phase, we will optimize the inflammatory co-culture model of enterocytes (Caco-2) with hepatocytes (HepG2). At the molecular level, we will analyze the ability of Lactobacilli to restore the impaired permeability of the Caco-2 monolayer and influence the inflammatory process and lipid metabolism in the model of inter-organ communication over time. We aim to contribute to elucidating the mechanisms underlying NAFLD development and the possibilities of its modulation by probiotics with our findings.

Role: active participant (laboratory work)

Grant UK/162/2023 Creation, analysis, and optimization of an in vitro model in a human HepG2 hepatocyte cell culture for studying inflammation-induced changes in hepatic mRNA expression of genes related to HDL.

The project was focused on the creation and optimization of an in vitro model in HepG2 cells using THP-1 monocyte-conditioned medium (CM). Due to its high content of proinflammatory cytokines and mediators, CM appears to be a suitable agent for inducing inflammation-driven changes in lipid metabolism in hepatocytes, as confirmed by mRNA expression changes in HepG2 cells exposed to CM.

Role: principal investigator